The Value of Pulmonary Artery Pressure-Guided Therapy for ...

The Value of Pulmonary Artery Pressure-Guided

Therapy for HF: Clinical Practice Experience

Maria Rosa Costanzo, M.D., F.A.C.C., F.A.H.A., F.E.S.C.

Medical Director, Advocate Medical Group-Midwest Heart Specialists

Heart Failure and Pulmonary Arterial Hypertension Programs,

Medical Director, Edward Hospital Center for Advanced Heart Failure

Naperville, Illinois, U.S.A.

DISCLOSURES: • Female Gender

• Born in Italy

• Lifelong Friend of Dr. Uri Elkayam

• Abbott: • Consultant

• Research Grants to the Advocate Heart Institute

• Steering Committee, CardioMEMS PAS Study

• Steering and Publications Committees, GUIDE-HF Trial

HF Hospitalizations Are a Strong Predictor of Mortality • Data from the EFFECT study,

n = 9138 patients1

• Among 1 year survivors after index EFFECT-HF discharge, the number of heart failure hospitalizations in the preceding year stratified the risk of death in crude analysis1

• Data from the Setoguchi et al., n = 14,374 patients2

• KP cumulative mortality curve for all-cause mortality after each subsequent hospitalization for HF2

4 1.Lee DS, et al. Am J of Med, 2009.

2.Setoguchi S, et al. Am Heart J, 2007.

Studies show each admission decreases a patient’s chance of survival.

Mechanisms of Worsening Heart Failure

5

Increased pressure is the proximate cause of congestion

Pressures rise early and have few confounders

Precipitating cause

Sympathetic activation Renal and dietary

Venous redistribution (fast)

Fluid retention (slow)

Increased L Heart Filling LAP/PAP

Pulmonary capillary transudation

Decompensation / hospitalization

Physiologic Markers of Acute Decompensation

6

* Graph adapted from Adamson PB, et al. Curr Heart Fail Reports, 2009.

Why Did Previous IHM Trials Fail? • Ill-defined and variably applied actions in response to

the monitoring information

• Lack of instructions on the appropriate care of patients who present for evaluation owing to a device alert

• Difficulty in assessing whether treatment decisions result from device monitoring information or are simply a consequence of the knowledge that the patient is in the Treatment arm of the trial (bias)

• Inadequate sample size

• Heterogeneous population and end-points

• Management based on single readings rather than trends

• Lack of protocol-based treatment guidelines and consequent variation between responses to the monitoring information

Sensor Home electronics unit

Systolic PAP

Mean PAP

Diastolic PAP

PA pressure trend data

Daily PA measurement

CardioMEMS-HF system: Ambulatory Hemodynamic

Monitoring with an Implantable PAP Sensor

Database

CHAMPION Clinical Trial: PA Pressure-guided Therapy Reduces HF Hospitalizations

9

Patients managed with PA pressure data had significantly fewer

HF hospitalizations as compared to the control group.

Abraham WT, Adamson PA, Bourge RC, Aaron MF, Costanzo MR, for the CHAMPION Trial Study Group. Lancet. 2011;377:658-666

Hemodynamic Management Treatment Group

Hemodynamic monitoring pressure ranges:

Pulmonary artery systolic pressure 15 – 35 mmHg

Pulmonary artery diastolic pressure 8 – 20 mmHg

Pulmonary artery mean pressure 10 – 25 mmHg


Costanzo MR, Stevenson LW, Adamson PA et al. Interventions Linked To Decreased Heart Failure Hospitalizations During Ambulatory Pulmonary Artery Pressure Monitoring; J Am Coll Cardiol HF 2016;4:333–44

Frequency of Medication Changes

Costanzo MR, Stevenson LW, Adamson PA et al. Interventions Linked To Decreased Heart Failure Hospitalizations

During Ambulatory Pulmonary Artery Pressure Monitoring; J Am Coll Cardiol HF 2016;4:333–44

BULLET GUIDE BULLET GUIDE

HEADER GUIDE HEADER GUIDE

Intervention Trial

Mean Duration

of Randomized

Follow-Up

Annualized Reduction

in HF Hospitalization

Rates

NNT per year to

Prevent 1 HF

Hospitalization

Beta-blocker COPERNICUS 10 months 33% 7

Aldosterone antagonist RALES 24 months 36% 7

CRT CARE-HF 29 months 52% 7

Beta-blocker MERIT-HF 12 months 29% 15

ACE inhibitor SOLVD 41 months 30% 15

Aldosterone antagonist EMPHASIS-HF 21 months 38% 16

Digoxin DIG 37 months 24% 17

Angiotensin

receptor blocker Val-HeFT 23 months 23% 18

Angiotensin

receptor blocker CHARM 40 months 27% 19

PA pressure monitoring CHAMPION 17 months 33% 4

CHAMPION Clinical Trial: The Number Needed to Treat (NNT) to Prevent One HF-related Hospitalization is Lower vs. Other Therapies


Cumulative HF Hospitalizations in Patients with HFpEF

Adamson PB et al. Circ Heart Fail. 2014;7:935-944

BULLET GUIDE BULLET GUIDE

HEADER GUIDE HEADER GUIDE

Comorbidity N size (control) N size (treatment) HF Hospitalization rate reduction at

15 months in treatment group

History of myocardial infarction1 137 134 46%

(p < 0.001 vs. control)

COPD2,3 96 91 41%

(p = 0.0009 vs. control)

Pulmonary hypertension4 163 151 36%


AF5 135 120 41%

(p < 0.0001 vs. control)

Chronic Kidney Disease6 150 147 42%


CHAMPION Clinical Trial: PAP-Guided Therapy Benefits Patients with Common HF Comorbidities

1. Strickland WL, et al. JACC 2011 2. Criner G, et al. European Respiratory Journal, 2012 3. Martinez F, et al. European Respiratory Journal, 2012 4. Benza R, et al. Journal of Cardiac Failure, 2012 5. Miller AB, et al. JACC, 2012 6. Abraham WT et al., HFSA 2014

Heart Failure Hospitalizations by GFR Quartiles

GFR Lowest to highest

Change in Pulmonary Artery Pressure Over Time Area Under the Curve (AUC) Analysis Stratified by GFR Quartile

Pulmonary Artery Pressure-Guided Therapy for

Ambulatory Heart Failure Patients in Clinical Practice: 1-Year Outcomes from the CardioMEMS Post-Approval Study

David M. Shavelle MD1, Akshay S. Desai MD, William T. Abraham MD, Robert C. Bourge MD, Nirav Raval MD, Lisa D. Rathman NP, J. Thomas J. Heywood MD, Rita A. Jermyn MD, Jamie Pelzel MD, Orvar T. Jonsson MD, Maria Rosa Costanzo MD,

John D. Henderson, Sandra A. Carey PhD, Philip B. Adamson MD and Lynne W. Stevenson MD for the CardioMEMS PAS Investigators

Circ Heart Fail. 2020; 13: e006863

Hospitalizations for HF Pre- and Post-Implant

1.24

0.52

0

0.2

0.4

0.6

0.8

1

1.2

1.4

HF

H R

ate

(even

ts/p

t-y

r)

1-Year Pre-Implant 1 Year Post-Implant

0.42 (0.38, 0.47)

p<0.0001

1.24

0.69

0

0.2

0.4

0.6

0.8

1

1.2

1.4

HF

H/D

eath

Rate

(even

ts/p

t-yr)


Hospitalizations for HF/Death

Pre- and Post-Implant

0.56 (0.51, 0.62)

p<0.0001

Hazard Ratio, 95% Confidence Interval and p-value estimated from the Anderson-Gill model. All hospitalization events adjudicated by CEC.

58% 44%

All-Cause Hospitalizations Pre- and Post-Implant


2.25

1.61

0

0.5

1

1.5

2

2.5

All C

au

se H

osp

italizati

on

(even

ts/p

t-y

r)

0.72 (0.67, 0.77)

p<0.0001

28%

Hazard Ratio, 95% Confidence Interval and p-value estimated from the Anderson-Gill model. All hospitalization events adjudicated by CEC.

Hospitalizations for Heart Failure: Pre- and Post-Implant

Stratified by Ejection Fraction

1.32

0.6

0

0.2

0.4

0.6

0.8

1

1.2

1.4

HF

H R

ate

(even

ts/p

t-yr)

0.46 (0.40, 0.52)

p<0.001 1.25

0.46

0

0.2

0.4

0.6

0.8

1

1.2

1.4

0.37 (0.29, 0.48)

p<0.001


1.12

0.44

0

0.2

0.4

0.6

0.8

1

1.2

1.4

EF < 40% (n=637) EF 41-50% (n=198) EF > 50% (n=363)

0.39 (0.32, 0.49)

p<0.001

54% 63% 61%

Heart Failure Hospitalizations: Pre-Implant vs Post-Implant Stratified by Planned Sub-Groups

All Subjects

(N=1200)

Gender Male 1.202 vs. 0.536 [748]

0.45 (0.39, 0.51)

Female 1.306 vs. 0.508 [452]

0.39 (0.33, 0.46)

Cardiomyopathy Ischemic 1.307 vs. 0.614 [496]

0.47 (0.40, 0.55)

Non-Ischemic 1.220 vs. 0.485 [449]

0.40 (0.33, 0.47)

Device ICD/CRT-D 1.284 vs. 0.579 [600]

0.45 (0.39, 0.52)

Without ICD/CRT-D 1.192 vs. 0.469 [598]

0.39 (0.33, 0.46)

Race White 1.192 vs. 0.483 [993]

0.41 (0.36, 0.46)

Black (of African Descent) 1.519 vs. 0.719 [172]

0.47 (0.37, 0.60)

Cells contain pre versus post-implant rates [sample size] / HR (95% CI) Results from Andersen-Gill model with rates as events/patient-years Reduced HFH Post-Implant

HR (95% CI)

Primary Safety Endpoints

Device/System

Related Complications 4/1214 (0.3%)

50%

60%

70%

80%

90%

100% 99.7%

80% OPC*

Freedom from Device/System Related Complications at 1 year

Sensor Failure

1/1200 (0.1%)

50%

60%

70%

80%

90%

100%

90% OPC*

99.9%

Freedom from Sensor Failure at 1 year

Sensor Failure: No readings can be obtained after troubleshooting system to rule out any problems with external electronics OPC* = objective performance criteria defined at 2 years

Device/System Related Complications: Adverse event that is possibly related to the system and has at least 1 of the following: treated with invasive means (other than IM medication or RHC), results in death of subject or results in explant of device. OPC* = objective performance criteria defined at 2 years

Change in Pulmonary Artery Pressure

Over Time (AUC) Through Two Years

Heart Failure and All-Cause Hospitalizations Rates

Pearls for the Implementation of a PAP-Guided Clinical Program

A Goal without a Plan Is Just a Wish Antoine de St. Exupéry

1. Create a clearly defined goal/vision To build a successful ambulatory hemodynamic monitoring program

2. Secure Sustained Support “From the Top”

3. Identify key champions to lead the process Physician champion –

NP/PA/PharmD Process champion –

Other key leaders with important influence Catheterization lab manager

Heart Failure unit nurse manager

HF clinic nurse supervisor

4. Define workgroup to design the program

Remote Monitoring Schema

Bhrambhatt, DH. Cardiac Failure Review 2019;5(2):86–92.

Patient Engagement and Education

Remote patient management (RPM) technologies are a Tool and NOT a Treatment

Important to identify patients who could benefit from RPM

Patient and caregiver engagement and education critical for success

Begin education patient and caregiver prior to implementing or implanting the technology

Review RPM data with the patient at each office visit

Anticipate and work through potential barriers to adherence

Summary Statements on The Value of Pulmonary Artery Pressure-Guided Therapy for Heart Failure:

Clinical Practice Experience

• Remote monitoring devices are non-therapeutic, but the actions taken in response to the data they provide can affect clinical outcomes.

• There is a close relationship between baseline PAP and risk of HF-related hospitalizations

• Changes in PAP occur before those in intra-thoracic impedance

• The designation of specific PAP targets and the adoption of consistent treatment strategies to achieve them are essential to the reduction of HF events.

• In the commercial setting, PA pressure-guided therapy for HF:

• Decreased PA pressures

• Decreased HF Hospitalizations

• across sex and race

• across all EF ranges

• on top of best medical and rhythm device therapies

• Decreased All-Cause Hospitalizations

• PA pressure-guided therapy was safe with few device/system related complications and a low rate of pressure sensor failure

• These benefits occur regardless of underlying comorbidities and pre-existing device therapy

• The use of PAP-guided HF therapy appears to be cost-effective

• In light of the facts summarized above wireless remote monitoring of PAP represents a true revolution in chronic HF management

The Value of Pulmonary Artery Pressure-Guided

Therapy for HF: Clinical Practice Experience

Maria Rosa Costanzo, M.D., F.A.C.C., F.A.H.A., F.E.S.C.

Medical Director, Advocate Medical Group-Midwest Heart Specialists

Heart Failure and Pulmonary Arterial Hypertension Programs,

Medical Director, Edward Hospital Center for Advanced Heart Failure

Naperville, Illinois, U.S.A.

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